Few neurological and neuropsychiatric disorders such as schizophrenia, attention deficit disorder (ADD), schizoaffective disorder, bipolar affective disorders and unipolar affective disorder have clinical manifestations that are correlated with demonstrable defects in the structure and/or function of the nervous system. Many of these disorders, however, involve subtle and/or undetectable changes in the cellular and molecular levels of nervous system structure and function. The lack of knowledge of the underlying anatomical or biochemical pathologies slows the development of new therapies for neurological and neuropsychiatric disorders. Rational correlations between these disorders and the underlying neurological signaling pathways have not yet been sufficient to enable the generation of new neurons and yield improved therapies to combat neurological and neuropsychiatric disorders.
New neurons are generated from neural stem cells, in two regions of the adult mammalian central nervous system: the subventricular zone of the lateral ventricle, and the subgranular zone of the hippocampal dentate gyms. Signals provided by the microenvironment contribute to the regulation of the maintenance, proliferation and neuronal fate commitment of the local stem cells. Many of these signals and signaling pathways are unknown.
The Disrupted In Schizophrenia 1 (DISC1) gene was initially identified as being disrupted by a balanced chromosomal translocation (1; 11) (q42; q14.3) in a large Scottish family with a high incidence of psychiatric disorders including major depression, schizophrenia and bipolar disorder. Subsequent studies provided indications, although no defined molecular/cellular mechanisms, that DISC1 may play a role in brain development.